Publications

The material below is provided to support scientific exchange. Any content about investigational therapeutics or investigational uses of locally approved products does not establish the safety or efficacy of these therapeutics or uses, and there is no guarantee of local regulatory approval.

For questions beyond a product’s authorized indications or for information not available here, please contact Alnylam Medical Information.

Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy and Renal Impairment: Analyses From HELIOS-B

Publication Details

Journal of Cardiac Failure

May 2026

Access Here

Author(s)

Farooq H Sheikh¹, Julien Dang², Marianna Fontana³, Vincent Audard⁴, Pablo Garcia-Pavia⁵, Michel G Khouri⁶, Antoine Jobbeé-Duval⁷, Yevgeniy Brailovsky⁸, Julian Gillmore³, Hua Zheng⁹, Satish Eraly⁹, Colleen Moffitt⁹, Ali Yilmaz¹⁰; HELIOS-B Trial Investigators

Affiliations

¹MedStar Heart and Vascular Institute/Georgetown University School of Medicine, Washington, DC; ²Assistance Publique des Hôpitaux de Paris, Hôpital Ambroise Paré, Service de Néphrologie, Boulogne-Billancourt, France; ³National Amyloidosis Centre, University College London, London, UK; ⁴Assistance Publique des Hôpitaux de Paris, Nephrology Department Henri Mondor Hospital University, University Paris Est Créteil, and National Institute of Health and Medical Research U955, Créteil, France;⁵Hospital Universitario Puerta de Hierro, IDIPHISA, CIBERCV, and Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; ⁶Duke University School of Medicine, Durham, North Carolina;⁷Médipôle Hôpital Mutualiste, Villeurbanne, France; ⁸Columbia University Irving Medical Center, New York, New York; ⁹Alnylam Pharmaceuticals, Cambridge, Massachusetts; ¹⁰Division of Cardiovascular Imaging, University Hospital Münster, Münster, Germany

Abstract

Background:

In HELIOS-B (HELIOS-B: A Study to Evaluate Vutrisiran in Patients With Transthyretin Amyloidosis With Cardiomyopathy), vutrisiran reduced the risk of all-cause mortality and cardiovascular events associated with ATTR-CM. We assessed the effects of vutrisiran on renal function and on outcomes by renal function.

Methods:

Patients were randomized to double-blind treatment with vutrisiran 25 mg or placebo every 3 months for ≤36 months. We evaluated the proportion of patients with a ≥40% decline in the estimated glomerular filtration rate (eGFR) from baseline and the primary composite end point (all-cause mortality or recurrent cardiovascular events) in subgroups based on baseline eGFR levels, and development of chronic kidney disease (CKD) stage ≥4 (eGFR <30 mL/min/1.73 m²) during treatment.

Results:

In HELIOS-B, 654 patients were randomized and treated with vutrisiran (n = 326) or placebo (n = 328). A ≥40% decline in the eGFR was seen in significantly fewer patients receiving vutrisiran vs placebo in the overall (12.7% vs 21.2%, P = .0041) and monotherapy (12.0% vs 21.9%, P = .0102) populations. The effect of vutrisiran on the primary composite end point in subgroups based on renal function was directionally consistent with the effect in the overall population. Among patients receiving vutrisiran vs placebo, 9.5% vs 9.8%, respectively, developed CKD stage ≥4. The risk of a primary composite end point event was significantly lower with vutrisiran vs placebo in patients who developed CKD stage ≥4 (hazard ratio 0.467, 95% confidence interval 0.258–0.845). No new safety concerns were identified.

Conclusions:

Vutrisiran may slow eGFR decline and is effective and well-tolerated in patients with ATTR-CM with declining renal function, including those developing CKD stage ≥4.